Editors' ChoiceGenetics

Genetic Basis for Variations in the Effect of Physical Activity on Cardiometabolic Risk

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Science Translational Medicine  19 Mar 2014:
Vol. 6, Issue 228, pp. 228ec48
DOI: 10.1126/scitranslmed.3008865

Have you ever wondered why exercise helps your metabolism? Is there a genetic basis for exercise-induced benefits on your health? Why response to physical activity is different between individuals?

A study conducted by Halder and coauthors asked exactly those questions. Investigators recruited middle-age adult volunteers to assess their individual peroxisome proliferator-activated receptor alpha (PPARA) gene polymorphisms on cardiometabolic risk in relation to physical activity. Both, PPARA and physical activity, affect lipids and glucose metabolism and vascular function; thus, understanding how they influence cardiometabolic risk in relation to each other is important. Cardiometabolic risk index for each individual was defined by using components of metabolic syndrome, whereas routine physical activity was assessed by using the Paffenbarger Physical Activity Questionnaire. Five PPARA single-nucleotide polymorphisms known for their association with obesity, diabetes, and cardiovascular risk were genotyped. Primary analyses were done by using a haplotype-based approach. As expected, higher physical activity was associated with lower cardiometabolic risk, whereas H-23 haplotype carriers had higher cardiometabolic risk. The most important finding of the study is that physical activity attenuated the negative effects of PPARA H-23 haplotype on cardiometabolic risk. This is the first investigation to demonstrate that PPARA variation interacting with physical activity affects cardiometabolic risk. The study provides specific evidence of a genetic basis underlying the individual effects of physical activity. Now, investigators have an example of how to proceed in researching interactions at genetic and molecular levels in order to study effects of physical activity on cardiometabolic risk.

I. Halder et al., PPARA gene polymorphisms modulate the association between physical activity and cardiometabolic risk. Nutr. Metab. Cardiovasc. Dis., published online 1 March 2014 (10.1016/j.numecd.2014.02.007). [Abstract]

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